1-substituted-4-[(tertiary-or secondary-amino)-alkylimino]-1, 4-dihydroquinolines



.nited States.

11 Claims. (Cl. 260-286) This invention relates to compositions of matter of the class of basic quinoline derivatives, to their acidaddition salts, and to the preparation of these compounds.

The invention here resides in a composition of matter selected from the group consisting of: (a) a 1,4-dihydroquinoline that is substituted by a lower-alkyl or a (monocarbocyclicaryl)methyl radical at the l-position and by a lower-(tertiaryor secondary-amino)-(polycarbon-loweralkyl)imino radical at the 4-position, and that can be further substituted from one to two substituents selected from the group consisting of a halo, lower-'alkoxy, loweralkylmercapto, lower-alkyl, nitro and trifiuoromethyl radicals at one of the normally aromatic positions of the quinoline nucleus; and (Z1) acid-addition salts thereof.

My compounds in free base form have the general Formula I lil Where Q represents H or from one to two substituents at positions 3, 5, 6, 7 and 8 of the quinoline' nucleus selected from the group consisting of halo, lower-alkoxy, lower-alkylmercapto, lower-alkyl, nitro and trifluoromethyl radicals, Y is a lower-alkylene radical having its connecting linkages on difierent carbon atoms, N=B is a member selected from the group consisting of lowersecondary-amino and lower-tertiary-amino radicals, and R is a member selected from the group consisting of lower-alkyl and (monocarbocyclic-aryl)methyl radicals.

In the above general Formula I the 'quinoline nucleus can be unsubstituted at the positions other than '1 and 4 or it can be substituted further at one of the normally aromatic positions of the quinoline ring, namely, 3, 5, 6, 7 or 8, by the substituents named above. When there are two substituents, they can be the same or difierent and can be in any of said available aromatic positions relative to each other. The halo substituents can be chloro, brorno, iodo or fluoro. The lower-alkoxy, lower-alkylmercapto and lower-alkyl substituents have preferably from one to six carbon atoms and include: methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, 2- butoxy, n-pentoxy, 'n-hexoxy and the like when loweralkoxy; methylmercapto, ethylmercapto, n-propylmercapto, isobutylmercapto, n-hexylmercapt'o and the like when lower-alkylmercapto'; and methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl and the like when lower-alkyl.

When representing a loWer-alkyl radical, R has preferably from one to six "carbon atoms and comprehends methyl, ethyl, n-propyl, is'opropyl, n-butyl, isobutyl, 2- butyl, 'n-pentyl, isopentyl, n-hexyl, and the like.

When representing a (monocarbocycli'c-aryl)methyl radical, R comprehends s'uch radicals where 'mono'carbocyclic-aryl, which can be designated as Ar, stands for an aryl radical 'of the benzene series. The aryl radical Ar includes the unsubstituted phenyl radical and phenyl atent ice radicals substituted by substituents including halo, nitro, lower-alkoxy, loWer-alkyl, loWer-alkylmercapto, trifluoromethyl, and the like. The substituted-phenyl radicals have preferably from one to three substituents including those given above; and, furthermore,'these substituents can be in any of the available positions of the phenyl nucleus, and where more than one substituent, they can be the same or diderent and they can be in any of the various position combinations relative to each other. Thus R comprehends the unsubstituted-benzyl radical as well as substituted-benzyl radicals illustrated by nitrobenzyl radicals including 4-nitrobenzyl, 3-nitrobenzyl, Z-nitrobenzyl, etc.; (lower-alkoxylated)-benzyl including 3-ethoxybenzyl, 2- methoxybenzyl, 2,4-dimethoxybenzyl, 2,4,6-trimethoxybenzyl, '3,4diethoxybenzyl, etc.; (lower-alkylated)-benzyl including 4-methylbenzyl, S-ethylbenzyl, 2-methylbenzyl, 2,4-dimethylbenZy1, 3,4,5-trimethylbenzyl, 4-isopropylbenzyl, etc.; halogenated-benzyl including 2-chlorobenzyl, 4-chlorobenzyl, 2,4-dibromobenzyl, 3-iodobenzyl, 2,4-dichlorobenzyl, 3,4-dichlorobenzyl, 2,4,6-trichlorobenzyl, 4- fluorobenzyl, etc.; and other substituted-benzyl radicals including 3-trifiuoromethylbenzyl, 4-methy1m'ercap'tobenzyl, and the like.

The lower-alkylene radical designated as Y preferably has from two to six carbon atoms including and the like. 7

'The amino radical, represented above as N=B, comprehends 'both pharmacodynamically acceptable lowersecondary-amino and lower-tertiary-amino radicals having preferably from one to about twelve carbon atoms. N=B thus comprehends lower-secondary-amino radicals and includes: mouocycloalkylamino radicals where the cycloalkylgroup has preferably '-from three to six ringcarbon atoms such radicals including cyclopropylamino, cyclobutylamino, cyclopentylamino and cyclohexylamino; mono-(lower-hydroxyalkyl)amino radicals where the lower-hydroxyalkyl group has preferably, two to six carbon atoms such radicals including Z-hydroxyethylamino, 3-hydroxypropylaniino, 4-hydroxybutylamino, Z-hydroxypropylarnino, 6-hydroxyhexylamino, etc.; mono-(loweralkyDamino radicals where the lower-alkyl group has preferably from one to six carbon atoms such radicals including methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, 2-butylamino, isobutylamino,

' n-amylamino, n-hexylamino, etc.; mono- E (monocarbocyclic-aryDmethyl] amino radicals where the (monocarbocyclic-aryDmethyl group has the meaning illustrated above for R, such radicals including benzylamino, 2- chlorobenzylamino, 3,4-dichlorobenzylamino, 3-nitrobenzylamino, 3 ,4-diethoxybenzylamino, 4-isopropylbenzylamino, 2,4,6-trichlorobenzylamino, etc.; and the like. The amino radical N=Balso comprehends lower-tertiaryamino radicals having two nitrogen substituents such as those illustrated above for the lower-secondary-amino radicals, with preferred tertiary-amino radicals being dilower-alkyD'arnino radicals where the lower-alkyl radicals are alike or difierent and each alkyl radical has preferably from one to sixcarbon atoms, such dialkylamino radicals including dimethylamino, diethylamino, ethylmethylamino, diisopropylamino, 'ethyLn-propylarnino, di-

'acceptahle anign l mean anyanionwhi v the animal organism inpharmacodynamic doses of the aceon'ra p s idyl, 3-ethyl-l-piperidyl, 4-methyl-l-piperidyl, 2,6-di methyl l -piperidyl; l-pyrrolidyl; (lower-alkylated) -lpyrrolidyl such as Z-methyl-l-pyrrolidyl, B-ethyl-l-pyrrolidyl, 2,5-dimethyl-l-pyrrolidyl; 4-morpholinyl; l-piperazyl; alkyl'ated-l-piperazyl such as 4-methyl-l-piperazyl, 4-ethy1-1-piperazyl, 2,4,6-trimethyl-1-piperazyl; and the like; 7 t My compounds in the form of their acid-addition salts can be written as having the general Formula II I l| l1'YN=B V l I II where Q, Y, N B and R have the meanings given above;

m is 1 or 2; and An is anranion. T e anion designated as An, which can be any phar- -mHA.n

. mace-dynamically acceptable anion, for instance, chloride,

acid-addition saltfso' that beneficial physiological properties inherent in the cation are not vitiated by any possible side-efiectsascribable to the anions; in other words, the latter do not substantially affect the pharmacodynamic properties inherent in the cations, f 7 iConcerning the structure of the acid-addition salts represented above as Formula'II, the'f ollowing considerations are presented. From chemical and physical data it appears'that structure 11 (where m is 1) is actually a resonance hybrid whose main contributing structures are represented as follows by A B:j

Art- Q An- V d (A); l (B) r Where m is 2 the situation is the same except that the second molecule of acid, HAn, is associated with the nitrogen atom of N=B. Since my cornpounds in free base form (Formula I) are readily obtained from their acidaddition salts by reaction with an acid-acceptonas shown below, and since theyare readily reconverted into their acid-addition salts by treatment with an acid, I, prefer, to represent the acid salt form by Formula II. As an illustration, I prefer to represent the monohydrochloride salt of 7-chloro-4(2-diethylaminoethylimino)-1 methyl-1,4-dihydroquinoline by the following structural Formula Ila:

' r r 4 H01 rir-cmcmmctnm Alternatively, this compound can be named 7-chloro-4- (Z-diethylaminoethylamino) l-methylquinolinium chloride or 7-chloro-4-(2 diethylaminoethylamino) quinoline monomethochloride and can be represented by the structural Formula IIb: i.

- sa m mmem 'N 0%: Cl

551 61: N All: t 5 ti Thus, it is to be understood that although I prefer to represent the acid addition salt form of my compounds by the'structur'al'formula designated above as 11, i.e.,flan acidaddition salt of a 1-substitutedi-4-(secondaryor tertiaryr .amino-alkylimino)-,1,4 dihydroquinoline where-m is 1,

this 4-imino-'l',4.-dihydroquinoline structure actually representsonly one of; the contributing members of 'a resonance hybrid; and, further, it is to be understood that the salt form of my invention comprehends not only this 4- imino-1,4-dihydroquinoline structure (as specifically illustrated above as IIa) but also other contributing members of the resonance hybrid including the l-substituted-4-(secondaryor tertiary-amino-alkylamino)-quinoliniurn' salt 7 structure (as specifically illustrated above as IIb) The compounds of Formula H are prepared by reacting the corresponding 4-haloquinolinium halide having the Formula HI where Q and R have the meanings designated above, An

is a halide ion and Hal is a chloro, bromo or iodo radical, with one molar equivalent of an alkylenediamine of the formula H N-Y--N=B and, if the compounds of For-v mula I'are desired, then reacting the resulting hydrohalide salt of the 1-substituted-4-(secondaryor tertiary-a mino-.- alkylimino) -l,4-dihydroquinoline (Formula II where m is l) with an acid-acceptor to yield the product in free base form (Formula I). Thus, the reaction of 1-(2-bromobenzyl)-4,7-diiodo-6-methoxyquinolinium iodide with I 2-diethylaminoethylamine yields the hydriodide of l-(2- bromobenzyl)-7-iodo-4-(Z-diethylaminoethylimino) 6- methoxy 1,4 dihydroquinoline which whenreacted with an acid-acceptor yields 1-(2 -bromobenzyl)-7-iodo-4-(2 diethylaminoethylimino) 6 methoxy-1,4-dihydroquino- 11:11 t, Y

- e step of reacting the-4-haloquinolinium halide (Formula III) with the alkylenediamine.H N Y'N=B is carried out' preferablyt 'by heating the reactants at a temperature between about 50,C. and 150C., preferably.

between about and 125 ?;C.; the7 reaction can be run at; room temperature; but it takes longer. The reaction is;

preferably carried out in an organic solvent which is inert under the conditions of the, reaction as for example,: ethanol, and the like. If an inert solvent is used, the product usually separatesafrom solutiontupon cooling,orn can be obtained by concentration of the solution.

The step of reacting the hydrohalide acid-addition salt,

(Formula H) with an acidacceptor is carried, out at room temperature or by heating, if necessary, up to a tempera-- ture of about C. The reaction is preferably carried. out in a solvent as for example, water or a lower-alkanoL' e.g., ethanolor methanol, or a mixture of water and a lower-alkanol. take up the hydrogen halide (or HAn) which is split out duringthe course of the reaction. The acid-acceptor is a. b25219 :ubstancel which preferably .forms freely water-.

The-purpose of the acid-acceptor'isto soluble by-products easily separable from the product of the reaction, including for example, sodium hydroxide,

potassium hydroxide, sodium carbonate, potassium car:

bonate, sodium acetate, sodium alkoxides, potassium alkoxides, sodium amide, and the like.

The compounds of Formulas I and H where R is a (monocarbocyclic-aryDmethyl radical, i.e., CH Ar, and where Y is CH CH and N=B is a lower-tertiary-amino radical can also be prepared by reacting the corresponding 4-(Z-tertiary-aminoethylamino) quinoline of the Formula IV w where Q has the meaning designated above, with one molar equivalent of an ester of the formula ArCH -An and reacting the resulting HAn acid-addition salt (Formula H: m is 1, Y is CH CH and N=B is lower-tertiaryamino) with an acid acceptor to yield the product in free base form (Formula I). Thus, 6,8-dimethoXy-4-[2-( lpiperidyl) ethylimino]-l-(2-methoxybenzyl) -l,4 dihydroquinoline is obtained by reacting 6,8-dimethoxy-4-[2-(lpiperidyl)ethylaminolquinoline with one molar equivalent of Z-methoxybenzyl chloride and reacting the resulting hydrochloride acid-addition salt of 6,8-dimethoxy-4- [2 (l piperidyl)ethylimino] 1 (2 methoxybenzyD- 1,4dihydroquinoline with an acid-acceptor.

The reaction of the 4-(tertiary-aminoethylamino)-quinoline (Formula IV) with onemolar equivalent of the ester ArCH -An is carried out by heating the reactants at a temperature between about 50 C. and 150 C., preferably between about 80 C. and 120 C. The reaction is preferably carried out in an organic solvent which is inert under the conditions of the reaction as for example, acetonitrile, acetone, ethanol, and the like. Ifan inert solvent is used, the product usually separates from solution upon cooling, or can be obtained by concentration of the solution. The reaction takes place most readily with arylmethyl esters ArCH -An Where An is the anion of a strong acid, e.g., halide, sulfate, phosphate, and the like. The chloride, bromide or iodide are preferred because of the more ready availability of the requisite arylmethyl halides.

The acid-addition salts of my compounds (Formula 11) where'An represents a halide ion are preferably prepared directly by theprocedures described above, which result in the formation of the monohydrohalides. The dihydrohalides are obtained by treating the corresponding monohydrohalides with a molar equivalent of a hydro.- halic acid. Salts where An is the anion of other strong acids or of a weak acid can be prepared by treating the corresponding compound in free base form (Formula I.) with the appropriate acid, or by treating an acid-addition salt (Formula II) prepared directly as noted above with an anion exchange resin saturated with the desired anion. Appropriate acid-addition salts are those derived from mineral acids including hydrochloric acid, hydrobromic acid, hydriodic acid, nitric acid, sulfuric acid and phosphoric acid; and organic, acids including acetic acid, citric acid, lactic acid, and tartaric acid. The acid-addition salts are prepared from the free base form (Formula I) by dissolving the base (1) in an aqueous solution containing the appropriate acid and isolating the salt by evaporating the solution, or by reacting the free base and acid in an organic solvent, in which case the salt separates directly or can be obtained by concentrating the solution.

Evaluation of the compounds of my invention by standard test procedures has shown that they have useful pharrnacodynarnic properties, such as hypotensive activity. Further, they are useful as intermediates, for example, in the preparation of some corresponding l-substituted-4- [lower (quaternary-ammonium) alkylimino] 1,4-dihydroquinoliues which are disclosed and claimed in my copending applications Serial No. 666,765, filed June 19, 1957 and Serial No. 666,785, filed June 19, 1957.

The following examples will further illustrate the invention, without the latter being limited thereto.

' EXAMPLE 1 g A. 4-[l0wer-(tertiqryor secondary-amino)-a lkylamino1- quinolines These intermediate compounds in the form of their free bases and acid-addition salts are generally known in the art. They are prepared by reacting the appropriate 4- haloquinoline with a diamine of the formula where Y and N=Bhave the meanings given above. New compounds of this type that I prepared as intermediates for the synthesis of the 4-[lower-(tertiaryor secondaryamino) alkylimino]-l-substituted'l,4-dihydroquinolines of my invention are given in Table A.

TABLE A CHQCHQN'HCH: 2HC1 l 250. 0-252. 2 CHzCH2NHC3H7-n 21101 l 278. 2-280. 6 CHzOHzNKiHal-a base a 121. 0-122. 8 CHzCH2N(CzH5)z 2HC1 279. 4-283. 0 CH (CH3) CHzCHzCHiNCtHsO d 154. 5-155. 0 CH:CH2N(CH3)2 b 252. 4 0151011 (02H 226. 4-228. 6 CH:CH CHzN(CHs)z 233. fi-fifi. 2 CH:CHzCH5N(C2H5): v 244. 6-247. 4 CHaCHzN(C4H9-11)2 2HsPO4..1 214. 6-217. 0 CHzCHzN (C2 6)! 2 H("1 219. 0-226. 4 CHzCHzN(OvHalo hash 67. 2- 73 4 CH2CH2N(C' hfiqP 116. 4-118 0 CH2CH2N(C2H5 126. 2-128 8 CH2CH2N(C2H1Q hflQP 94. 8'- 98 8 CHzCH2N(CHa)z. 211C! 224. 8-227 0 CHzCH2N(CzHs)1 2HC1.HaO t 135. 6-133 8 CHgCHmKhHfla 2HC1 138. 6-143 6 CHQCHzNKCrHs h9g4 0-103 6 b With decomposition.

- Base and diphosphate shown by Surrey et 81., JAOS 68, 113 (1946). NC4H|0-4-morpholinyl.

' quinoline, and 2-chlorobenzyl :chloridefandthe' Iik The acid-addition salts of thebasic quinolines of Table A.were converted into their 'freebase' form for useas intermediates in the "preparation of the compounds of the invention. was done by dissolvingthe salt in water, adding an alkaline agent such as. ammonium hyidroxi'de to the aqueous solution to liberate .the'basic by reaction with an acid-acceptor according to the pro; cedure' given in Example 2 for .the conversion of 7} quinoline, extracting'the basic quinoline with'f an organic solvent such as chloroform and removing the organic.

solvent by distilling in vacuo to leave the basic quinoline.

. l-arylmethyl 4 [lower (tertiaryarnino) ethyl;

V V imin'o]1,4-dihydr0quin0lines The preparation of thesecompound-s injthe form's: their acid-addition salts is illustrated by the following preparation'of the hydrochloride of 7-chloro-1-(2-chloroybenzyl)-4 2 diethylaminoethylimino) 1,4 dihydroquinolinez' A solution-containing 5.0 g. of 7-chloro-4- (2rdiethylaminoethylamino)quinoline, 2.9 g. of 2-chlo'robenzyl' chlorideand 25 cc. of acetonitrile was refluxed, for. five hours and then cooled to about 6 C. and allowedto stand forty-eight hours. The precipitate was collected and recrystallized from acetonitrile to yield 3.4 g (43% yield) of the product, 7 -ch1oro-l-(2-chloroben'zyl)-4-(2-diethylaminoethylimiho) 1,4- dihydro quinoline hydrochloride, M.P. -l94.0207.6 C. "(corr.).

Analysis.-Calcd. for C H Cl N 'I-ICl: Cl", 8.08; N;

9.58. Found: Cl, 7.77;N, 9.63. Alternatively, as discussed hereinabove', 7-chloro-1- (2-chlorobenzy-l)-4 (2 diethylaminoethylimino) 1,4

Other 1 arylmethyl 4 [lower (tertiary-amino} ethylimino]-1,4-dihydroquinolines that can. be prepared following the above procedure using one molarequiva= lent each" of the appropriate 4-(tertiary-aminoethylamino-)-quinoline and arylmethylester of a strong acid includef 6,7 dichloro 4 [2 (1 piperidyDethyl- V imino] 1 .(2 methoxybenzyl) 1,4 dihydroquinm 'line hydrochloride using 6,7-dichlor0-4-[2-(1-piperidyl)- ethylaminolquinoline and 2-methoxybenzyl chloride; 7- bromo -'4 1 (2 di n hexylaminoethyliminmf 1- (2,4 dimethoxybenzyl) "1,4; dihydroquinoline hydro-.

bromide using 7 bromo '4 (2 4 di n 1 hexylaminoethyl-amino) quinoline and 2,4 dimethoxybenzyl bro- -dihy'droquinoline hydrochloride canbe called"7-chlorothyliinind) '1,4"- dihydroquinoline hydrochloride into its "corresponding *free base' by jreaction with" aqueous 7 7 -ch loro-l (2-chlbrobenzyl)-4-(2-diethylamiriothyl- 7 imino)-1,4dihydroqui olirle V Thirty grams of 7-chloro-1-(2-chlorobenzyl) 4 (2-di; ethylaminoethylirnino)quinoline hydrochloride were dissolved in 400 cc. of warm water. The solution was made basic by the slow addition of 74cc. of 10% aqueous sodium hydroxide solution... The oil which separated solidified on cooling and triturating. The solid was recrystallized from n-hex'ane, to yield 22.9 g. (83% yield) of the product, 7-chloro-l-(2achlorobenzyl)-4-(2- diethylaminoethylimino) -"1,4 dihydioquinolin'e, M.P.

. 106.0l07.6 C. (corr.).

" Analysis.-'--Calcd. for C H Cl N 'Cl, 17.63; N, 10.44. Found: Cl, 17.46; N, 10.27. Treatment of 7-chloro-l-(2-chlorobenzyl)-4-(2-dieth ylarninoethylimino) quinoline with an excess of ethanolio cedure describedinExample 1B using'5 g. of '5-ch1oromide;1 (2,4 dibromobenzyl) 4 [2 (N ethyl- N 2 hydroxyethylamino)ethylimihol 3 nitro 1,4- dihydroquinoline hydrobromide using-4 [2 (N ethyl- N 2 hydroxyethy1amino)ethylamihd] 3'- nitroquinoline and 2,4 dibromobenzyl bromide; l -(2 chloro-4- methoxybenzyl) 6,8 dimethoxy 4'- [2- (4 methyl 1 piperidyl)ethyliminol '1,4 dihydroquin'oline hydrochloride. using 6,8 dirnethoxy 4:- [2 (4 methyl 1 a peri y )et arn olxu o ne. and..2.;.. hl .;.41 methoxyhenzyl chloride; 4 [2 (N benzyl 7 N ethylamiilo) ethylimino] 8 n butoxy l (2,4,6 trichlorobenzyl) 1,4 "dihydroqui-neline hydrochloride using 4 [2 (N .benzyl -..N;.-.ethylamino,) ethylamino1- S-n butOXyquinoline and 2,4;6-trichlorobenzyl chloride;

4. [2 (4.- .niorpholinyDethyliminoII .6- n hexoxyl ('3 trifluoromethylbenzyl) '1,4 dihydroquinoline hydrochlorideii'lu'sing 4-[2-(4-morpholinyl) ethylaminol-j dn-hergoxyquinoline and *3 trifiuoromethylbenzyl chlo- "ride; .1 (2 -Ichlorobenzyl):-'4LQI2;(N 7 ethyl N- m t mhy im :i8i;-.; rqbatylm dihydroquinolinehydrochloride using.4 I2 (N ethyl- 'N '-,methylaminqethylamino] 8 isobutylmercaptochloro" 4" (2-= 'diethylarninoethyl amino) 6- methoxy' 4-(2-diethylaminoethylamino) quinoline,j2.9 g. of"2-chlo-' robenzyl chloride, 25 .cc. of acetonitrile and a reflux period of twelve hours. There was thus obtained. 5.4g. (68% yield) of the product, 5-chloro51-(2-chlorobenzyl)-. 4 (2 -.diethylaminoethylimino) 1,4 -'dil1ydroquinoline. hydrochloride, M.P. E 205 .0" C. (corn) with .decomposition when recrystallized from isopropanol. 1 Analysis.--Galcd. for C H Cl N .HCl: Cl, 8.08; N, 9.58. 'Found: H O, 3.64; Cl, 7.96 (dry basis); N,- 9.50 (dry :basis ).1.. EXAMPLE 4 j'" e 7 -'chlor0 1"' -(2 chZ0robenzyl)"-"4 '[2 L (N 5 2 chlorobenzyl N ethylamino) ethylimino] 1,4-

dihydroquinoline hydrochloride a This preparation was carriedaoutfollowinglthe procedure described in Example 1B using 3.0 g. of 7-chloro- 4 [2 (N 2 chlorobenzyl N ethylamino)ethyl- 'aminolquinoline, 1. 6 g. of 2-chlorobenzylchloride, 25

m-.. ..cc...nfn.acetonitrile and a reflux period of twenty-four hours. There was thus obtained 2.6 g. (59%. yield) of These compoundsfare converted. intoztheir freebase 'form the product, 7 chloro 1 (2 chlorobenzyl) 4 [2- "(N 2 chlorobenzyl N, ethylamino) ethylimino] l, 4-dihydroquinoline hydrochloride, M.P. 199.-820l.4 C. jj(cor r.) when recrystallized once from acetonitrile and once from isopropanol.

7.35. Found: c1, 26.37; N, 7.92. 7

EXAMPLE 5 17 chloral 1 2 chlorobenzy l) .4 r2 4 morpholinyl)ethylimin0] 1,4-dihydr0quinoline hydrochloride fljj'l'hi's preparation was carried'out; following the pro "eedure described in Example 1 B using 5.0 g. of 7-chloro- 1:41-12 ('4 morpholinyhethylamino] quinoline, 2.4 g. of --2-'chlorobenzyl chloride, 25 cc. of acetonitrile and a reflux period of twenty-four hours. tained; g. *yield) of product, 7-chloro-l-(2- There was thus obstirring.

ii chlorobenzyl) 4 [2 (4 morpholinyDethyliminol- 1,4-dihydroquinoline hydrochloride, M.P. 238.2241.2 C. (corn).

Analysis.-Calcd. for C H Cl N HCl: Cl", 7.83; N, 9.28. Found: Cl-, 7.80; N, 9.12.

EXAMPLE 6 A. I-arylmethyl-4-haloquinolinium halides The preparation of these intermediates is illustrated by the following preparation of 7-chloro-1-(2-chlorobenzyl)-4-iodoquinolinium iodide: a reaction mixture containing 80 g. of 4,7-dichloroquinoline, 128 g. of 2- chlorobenzyl chloride, 177 g. of sodium iodide and 1200 cc. of acetone was refluxed for twenty-four hours with The reaction mixture was allowed to cool and the precipitate was collected; washed successively with acetone, water and acetone. There was thus obtained 130 g. (60% yield) of 7-chloro-1-(2-chlorobenzyl)-4- iodoquinolinium iodide, M.P. 208-209 C. (uncorr.).

Following the above procedure using an equivalent quantity of 4,5-dichloroquinoline in place of 4,7-dichloroquinoline, the product obtained was S-chloro-l-(Z-chlorobenzyl)-4 iodoquinolinium iodide, M.P. 201-202 C. with decomposition.

Anal.Calcd. for C H cl lNl-llz C, 35.45; H, 2.04; I", 23.42. Found: C, 35.28; H, 2.30; 1', 25.6.

Other l-arylmethyl-4-haloquinolinum iodides that can be prepared following the above procedure using the appropriate 4-haloquinoline, benzyl halide and sodium iodide include: 3,7-dichloro-4-iodo-1-(3-nitrobenzyl) quinolini- 11m iodide using 3,4,7-trichloroquinoline, 3'nitrobenzyl chloride and sodium iodide; 7-bromo-1-(2,4-dimethoxybenzyl)-4-iodoquinolinium iodide using 4,7-dibromoquinoline, 2,4-dimethoxybenzyl bromide and sodium iodide; 8-chloro-4-iodo-1-(2,4,6-trimethox;ybenzyl) quinolinium iodide using 4,8-dichloroquinoline, 2,4,6-trimethoxy-ben- Zyl chloride and sodium iodide; l-(3-ethy1benzyl)-4-iodo- 7-trifluoromethylquinolinium iodide using 4-iodo-7-trifluoromethyl-quinoline, 3-ethylbenzyl chloride and sodium iodide; 4-iodo-7-methylrnercapto-1- (2 methylmercaptobenzyl)quinolinium iodide using 4-chloro-7-methylmercaptoquinoline, Z-methylmercaptobenzylchloride and sodium iodide; and the like.

B; 7-chloro-1-(Z-chlorobenzyl)-4-(Z-dimethylaminoethylam inoethylimino) ,4-dihydroquin0line dihydroch loria A solution containing 5.28 g. of Z-dimethylaminoethylamine in 50 cc. of absolute ethanol was heated and treated portionwise with stirring with 11 g. of 7-chloro-1(2- chlorobenzyl)4-iodoquinoliniurn iodide. When a clear solution had resulted, it was cooled. The resulting precipitate was collected and recrystallized from ethanol-water to yield 7.5 g. (73%) of 7-chloro-1-(2-chlorober1zyl) 4- (Z-dimethylaminoethylimino)-1,4-dihydroquino1ine hydriodide, M.P. 230231 C. (uncorr.). This hydriodide salt was converted to the corresponding imino base by dissolving 3.5 g. of it in ethanol-water and treating the re: sulting solution with excess 5% aqueous sodium hydroxide solution. Addition of water yielded a precipitate which was collected, the yield being 2.7 g. (100%) of 7- chloro-l-(2-chlorobenzyl) 4 (2 dimethylarninoethylimino) -1,4- dihydroquinoline, M.P. 144145 C. (uncorn).

Other 1 arylmethyl-4(tertiary-aminoalkylimino)-1,4- dihydroquinolines that can be prepared following the above procedure using the appropriate l-arylmethyl-4- iodoquinolinium iodide and tertiary-aminoakylamine include: 3,7 dichloro-4-(4 diethylaminobutylimino)-1-(3- nitrobenzyl) -1,4-dihydroquinoline using 3,7 dichloro 4- iodo-1-(3-nitrobenzyl)quinoliniurn iodide and 4 diethylaminobutylamine; 7 bromo 4 2- diethylaminoethylimino)-1-(2,4dimethoxybenzyl)-1,4 dihyroquinoline using 7-bromo-I-(ZA-dimethoxybenzyl)-4-iodoquinolinium iodide and 2-diethy1amino-ethylamine; 8-chloro-4-.[3-( 1-, pyrrolidyDpropyliminol-1-(2,4,6 trimethox-ybenzyl) 1,

4 dihydroquinoline using 8 chloro 4-iodo-1-(2,4,6-trimethoxybenzyl)quinoliniurn iodide and 3'- (-1-pyrrolidyl)- propylamine; 4-(3-diethylamino-2 propylimino) 1 (3- ethylbenzyl)-7-trifluorornethyl-l,4-dihydroquin0line using 1-(3-ethylbenzyl)-4-iodo 7 trifluoromethylquinolinium iodide and 3-diethylamino-Z-propylamine; 4-[3-(N-cycloheXyl-N-methylamino)propylimino] 7-methylmercapto- 1-(2-rnethylmercaptobenzyl)-1,4-'dihydroquinoline using 4-iodo-7-methylmercapto 1 (Z-methyImercaptobenzyl) quinolinium iodide and 3-(N-cyclohexyl-N-methylamino) propylamine; and the like.

7-chloro-1-(Z-chlorobenzyl) 4 (2 dirnethylaminoethylimino)-l,4-dihydroquinoline (2.7 g.) in isopropanol solution was treated with ethanolic hydrogen chloride until the solution was acidic. The solution was cooled and the resulting precipitate was collected and recrystallized from isopropanol to yield 2.3 g. (65%) of product, 7- chloro-l-(Z-chlorobenzyl) 4 (2 dimethylarninoethylimino)-1,4-dihydroquinoline dihydrochloride in the form of its monoisopropanolate, M.P. 253.8255.4 C. (corn).

Anal;Calcd. for C H Cl N .2HCl.C H-,OH: Cl, 27.96; N, 8.28. Found: H O, 1.30; CI, 27.90 (D.B.); N, 8.50 (D.B.).

By substitution of the hydrogen chloride in the preceding example with an excess of hydrogen bromide, phosphoric acid, sulfuric acid, tartaric acid or methanesulfonic acid, there can be obtained 7-chloro-1-(2-chlorobenzyl)-4-(Z-dimethylaminoethylimino) 1,4 dihydroquinoline dihydrobromide, diphosphate, disul-fate, ditartrate or dimethanesulfonate, respectively.

EXAMPLE 7 7-chl0ro-1'-( 2-chlor0benzyl) -4- (2-di-n-butylaminoethylimino) -1,4-dihy droquinoline hydrochloride This preparation was carried out following the pro cedure described in Example 113 using 1.15 g. of7-chloro- 4-(2-di-n-butylaminoethylamino)quinoline, 0.54 g. of 2- chlorobenzyl chloride, 25 cc. of acetonitrile and a reflux There was thus obtained 1.06 g. (62% yield) of the product, 7-chloro-1-(2-chlorobenzyl)-4-(2-di-n-butylaminoethylimino) 1,4 dihydroquinoline hydrochloride, M.P. 179.2-183.2 C. (corn) when recrystallized from acetone.

Anal.-Calcd. for C I-I Cl N .HCl: Cl, 7.17; Cl, 21.51. Found: Cl, 7.13; Cl, 21.03.

EXAMPLE 8 S-chloro-I- (2-chl 0robenzyl) -4-(Z-di-n-butylaminoethyl; imino) -1-,4-dz'hydr0quin0l ine hydrochloride This preparation was carried out following the procedure described in Example'lB using 2 g. of 5-chloro-4- (Z-di-n-butylaminoethylamino)quinoline, 1 g. of 2-chlorobenzyl chloride, 50 cc. ofacetonitrile and a reflux period of twenty-four hours. There was thus obtained 1 g. (34% yield) of the product, S-chloro-l-(Z-chloroberlzyl)- 4-(2-di-n-butylaminoethylimino) 1,4 dihydroquinoline hydrochloride, M.P. 206.8-207.7 C. (corn) when recrystallized from acetonitrile-ethyl acetate. AnaL-Calcd. for C H Cl N .HCl: 8.49. Found: Cl, 21.36; 'N, 8.20.

EXAMPLE 9 .5-chlor0-1 -(2-ch lorobenzyl) -4- [2- (4-morpholinyl) ethyl- I imino] -1,4-dihydroquin0line hydrochloride This preparation was carried out following the procedure described in Example 1B using 5.0 g. of S-chloro- 4-[2-(4-morpholinyl)ethylamino']quinoline, 2.42 g. of 2- chlorobenzyl chloride, 25 'cc. of acetonitrile and a reflux period of twentyafour hours. There was thus obtained 6.3 g. (82% yield) of the product, 5-ehloro-1-(2 -chlorobenzyl)-4-[2-(4-morpholinyl)ethyl-imino] 1,4dihydroquinoline hydrochloride, M.P-..215.6-221.4" C. (corn) when recrystallized from ethanol-ethyl acetate. 7 Y

ArtaL-Calcd. for 'C gH- Cl N O.HC1: Cl", 7.83; N, 9.28. Found: C1-, 7.72; 'N, 9.02.

chloridc'ions (Amberlite IRA-400).

. 11 EXAMPLE 10 f f meth xy-I,4-dihyldroq11iizoline hydrochloride This preparation was carried out following the procedure described in Example 1B using 5.0g. of 4-(2-di- .ethylaminoethylamino).-6-methoxyquinoline, 2.7 g. of 2- chlorobenzyl chloride',g25 ccgof acetonitrile and areflux period of twenty-four hours. There was thus obtained 4.7 g. (59% yield) of the product, 1-(2-chlorobenzyl)-4- (Z-diethjzlaminoethylimino) -6-,methoxy- 1 ,4-dihydroquinoline hydrochloride, M.P. 223.8-2284" C. (corn) when recrystallized from isopropanol. 1

AjzaLCalcd. for CggH C1-N QHCl: Cl-,, 8.16; N, 9.67. Found: Cl-,- 8.00;;N, 9.64. e

EXAMPLE 11 7-ch Zora-1 2 -ch lorobenzyl -4 3 -di m ethylaminopropylimz'no)-1,4-dihydroquin0line dihydrochloride .This preparation was carried out following the procedure described in Example 6B using 11 got 7-chloro-l- (2-chlorobenz'yl)-4'iodoquinolinium iodide, 6.3 g. of 3 dimethylaminopropylamine and 50 cc..of absolute ethanol. There was, thus obtained 7.5 g. (71% yield) of 7-chloro- 1 f( 2-chlorob enzyl '4-( 3 -'dimethylaminopropylirnino) l ,4-

dihydroquinoline hydriodide, M.P. 210-211 C. (1111- corn).

l f'lhe hydriodide 3 g.) was dissolvedin ethanol-water and treated with excess 5% sodium hydroxide solution to give 2 g. of 7 chloro 1 (2 chlorobenzyl) 4 (3 di- .methylaminopropylimino) 1,4 dihydroquinoline, M.P.

67- -68- C. (uncorn). This imino base was converted into its dihydrochloride following the procedure given in Example 6B. There was thus obtained 1.5 g.,(55% yield) of 7 chloro l (2 chlorobenzyl)-4-(3-dimethylaminopropylimino)-1,4-diliydroquinoline dihydroc'hlon'de, M.P.

24l.8 246.8 C. (com) with decomposition when re-' swa 12 r r o v -EXAM'PLE1 3'@ j "1 7-cl1l0ro-l (Z-ChIoflobenzyl -5 (5 -diethylami nbpertltylimino) J,4-dihydrquinoline'dihydrochZoride 7 This preparation was carried out following the procedure described in Example 11 'using 5.4 g. of 7-chloro-l- (Z-chlorobenzyl) 4-iodoquinoliniumiodide, 5.0 g. of diethylaminopentylarnine and,5:0 cc. of absolute ethanol. There was'thus obtained 7-chloro-l-(2-chlorobenzyl)-4 V (5 diethylaminopentylirnino) l',4- dihydroquinoline hytime was warmed 'on a steam bath jnntil-all'of'the solid had-dissolved and the "resulting-solution was-"chilled; in V an icebath. "The resulting'precipitate was'collected' and dried; therebeing obtained 10.0 g. (78%fy'ield) of the product, 7-ch1oro1-(2-chlorobenzyl)-4-(4-diethylamino butylimino)-l,4dihydroquinoline hydriodide, M.P. 188- 191C. (uncorn).

r -i B. 7-c hloro-1 -(2-chlorobnzyl)-4-(4-diethylamin0- butylimino) -1,4-dihydr0quinoline hydrochloride 7 ichloro '1 (2 chlorobenzyl) 4 (4-diethylaminobutylimino)-l,4-dihydroquinoline hydriodide (8.3 g.) was dissolved in 500 cc. of 50% ethanol and passed over a column of 30 g. of an ion-exchange resin saturated with v The column waseluted with water and the combined eluants were distilled in'vacuo to remove all of the solvent. The remaining solid was. recrystallized fromjisopropanol' to yield 2.9 g. (42%) .of product, 7-chl0ro-l-(2-chlorobenzyl)-4- (4-diethylaminobutylimino) -l,4rd hydroquino' line hydrochloride, M.P. 216.8-226.4 C. '(corr.)'.-

A nal. 3 aled. for V C H Cl N .HCl: 101%,; 7.60;] N, 9.00. Found: Cl", 7'.'$2;'N,.8.90. 1

compounds in free'base form.

- F und N eon N, 9.03.

driodide which was converted into its imino base and then into the corresponding dihydrochlon'de, 'M'.P. 231.8

This preparation was carried out following-the procedure described in Example 11 using 14 g. of 7-chloro-.1-'

(2-chlorobenzyl)-4-iodoquinolinium iodide, 7.8 g. of 6- diethylaminohexylamine and 50 cc. of ethanol. There was thus obtained 10 g. (75% yield) of 7-chloro-1 (2- chlorobenzyl) 4-(6 -diethylaminohexylimino)-1,4-dihy droquinoline hydriodide which was converted in yield to the corresponding imino compound. This product, 7-chloro-l (2chlorobenzyl)-4-(6-diethylaminohexylimino)el,4-dihydroquinoline, melted at 87.0-88.2 C. (corn) when recrystallized from ethanol-water. Anal.-Calcd: for lC I-I Cl N N 6.12; N, 9.18.

EXAMPLE 1s- 7-c hlor 'o-1-(2 -chlorob enzyl)-4-(2-methylamin,oethylimino) -1,4-dihydroquinoline dihyah ochloride Following the procedure described in Example 11 using 5.4 g. of 7-chloro-1-(2-chlorobenzyl)-4-iodoquino]inium iodide, 7.5g. of Z-methylamindethylamine and'60 cc. of absolute ethanol. 'Ther'e was thusobtained 3.5' g. of 7- chloro-1-(2.-chlorobenzyl) =4-( 2-methylaminoethylimino) 1,4-dihydroquinoline hydriodide, M.P. 219-220 C. (uncorr.) when recrystallized from ethanol; r 7

:The above-described hydriodide (3.5 g.) was ion-exchanged over 18.g. o anion-exchange resin saturated with chlorideions (Amberlite IRA-400 resin), said resin suspended in hot methanol. .There was thus;ohtained 1.7 g. (61% yield) of 7-chloro-l-(2-chlorobenzyl.) 4 (2 methylaminoethylimino)-1,4-clihydroquinoline hydrochloride, 0.9 g. of which was dissolved in absolute ethanol and treated with excess ethanolic hydrogen chloride to give 0.5g. of 7-chloro-1-(2-chlorobenzyl-)-4-(2 methylaminoethylimino)-l,4-dihydroquinoline dihydro chloride, M.P. 226.8228. 6 C. (corn). 7 V

Anal.--Calcd. for C l-I gCl N lHClz Cl: 16.37; N,- 9.70. Found: 01-, 16.18;. N, 9.60. V By substitution of the ,2-methylaminoethylamine in the preceding example with an equivalent amount of 4-cyclo hexylaminobutylamine, 73-n-propylaminopropylamine or Z-n-hexylaminoethylamine, there can be obtained respectively, 7-chloro-1-(2 chlorobenzyl)-4-(4-cyclohexy1arnino butylimino) 1,4 dihydroquinoline dihydro chloride, 7- chloro-1-(2-chlorobenzyl)-4'- (3 n'- propylaminopropyl imino)-l,4-dihydroquinoline dihydrochloride or 7-chlor0- 1- (2-chlorobenzyl) -4- 2-n-hexylani'moethylimino) -1 ,4-dihydroquinoline dihydrochloride. Treatment of these di'-' hydrochlorides with an acid-acceptor according to'the: procedure described in Example-2 yields thelrespective 13 EXAMPLE 16 7-chloro 1 (2 chlorobenzyl) 4 [2-(2-hydr0xyethylamino)ethylimin] 1,4 dihydroquinoline dihydrochloride A mixture of 27 g. of 7-chloro-1-(2-chlorobenzyl)-4- iodoquinolinium iodide in 200 cc. of ethanol was stirred and warmed on a steam bath while 21 g. of 2-(2-hydroxyethylamino)ethylamine was added. When the reactants had dissolved, the resulting solution was filtered and allowed to stand at room temperature overnight. The precipitate was collected and dried, yielding 25 g. (97%) of 7-chloro-l-(2-chlorobenzyl) 4-[2-(2-hydroxyethylamino) ethylimino] -1,4-dihydroquinoline hydriodide, M.P. l77-l78.5 C. (uncorn) when recrystallized from ethanol.

The above hydriodide was dissolved in a minimum amount of ethanol and a molar equivalent of 6N ethanolic hydrogen chloride was added. The solution was cooled to yield a precipitate which was collected; this was 7- chloro-l-(Z-chlorobenzyl) 4-[2-(2-hydroxyethylamino) ethylimino] 1,4 dihydroquinoline hydrochloride hydriodide, M.P. indefinite.

A solution of this hydrochloride hydriodide in aqueous ethanol (two parts of ethanol) was run through an ionexchange resin containing an excess of chloride ions (Rohm and Haas Amberlite IRA-400 resin); and the eluant was evaporated in vacuo yielding the solid product, 7-chloro-1-(2-chlorobenzy1)-4-[2 (2 hydroxyethylamino) ethylimino] -l ,4-dihydroquinoline dihydrochloride, M.P. 2168-2192 C. (corr.).

Analysis.-Calcd. for C H Cl N 02HCl: 01-, 15.20; N, 9.06. Found: Cl, 15.04; N, 9.01.

By substitution of the 2(2-hydroxyethylamino) ethylamine in the preceding example with an equivalent amount of 3-(3-hydroxypropylamino)propylamine, 2-(4-hydroxybutylarnino)ethylamine or 4 (Z-hydroxypropylamino) butylamine, there can be obtained, respectively, 7-chloro- 1-(2 chlorobenzyl)-4 [3 (3 hydroxypropylamino) propyliminoJ-1,4 dihydroquinoline dihydrochloride, 7- chloro-1 (2 chlorobenzyl) 4 [2-(4hydroxybutylmino)ethylimino] -1,4 dihydroquinoline dihydrochloride or 7-chloro-1-(2-chlorobenzyl%4 [4(2-hydroxypropylamino) butylimino] 1,4 dihydroquinoline dihydrochloride. Treatment of these dihydrochlorides with an acidacceptor according to the procedure described in Example 2 yields the respective compounds in free base form.

EXAMPLEv 17 7-chl0ro 1 (2,4 dichlorobenzyl) 4 --(2-diethylamin0- ethylimino) 1,4 dihydroquinoline hydrochloride This preparation was carried out following the pro cedure described in Example 1B using 10.0 g. of 7-chloro- 4-(2-diethylaminoethylamino)quinoline, 7.0 g. of 2,4-dichlorobenzyl chloride, 50 cc. of acetonitrile and a reflux period of five hours. There was thus obtained 7.3 g. of 7-chloro 1 (2,4 dichlorobenzyl) 4-(2-diethylaminoethylimino) 1,4-dihydroquinoline hydrochloride, M.P. 231.4236.8 C. (corn) when recrystallized from isopropanol and dried in a vacuum over for seventy-two hours.

Analysis.Calcd. for C H Cl N l-ICl: Cl", 7.49; N, 8.88. Found: Cl", 7.52; N, 8.60.

EXAMPLE 18 A. 1 (lower-alkyl) 4 haloquinolinium halides The preparation of these compounds is illustrated by the following synthesis of 7 chloro 4-iodo-1-methylquinolinium iodide: A reaction mixture containing 40 g. of 4,7dichloroquinoline, 57 g. of methyl iodide and 400 cc. of acetone was allowed to stand at room temperature for four days. The solid which had separated was collected and recrystallized from methanol-water, yielding 33 g. (38%) of 7 chloro-4-iodo-l-methylquinolinium iodide, M.P. 265-266" C. (uncorr.) with decomposition.

1d Analysis.-Calcd. for (2 14 011 14; 0, 27.82; H, 1.86; I", 2993. Found: C, 28.08; H, 1.86; I", 30.50.

When the above reaction was repeated using twice the quantity of methyl iodide and 29' g. ofsodium iodide, the yield was 56 g. (65%), M.P. 264-265 C. (unconz).

By substitution of an equivalent quantity of 4,5-dichloroquinoline for 4,7-dich1oroquinoline in the above procedure, the product obtained was 5-chloro-4 iodo-1- methylquinolinium iodide, M.P. 248-250 C.

Other l-(lower-alkyl)-4haloquinolinium iodides that can be prepared following the above procedure using the appropriate 4-haloquinoline and lower-alkyl iodide (or other lower-alkyl halides and sodium iodide as in Example 6A) include: 3,7 dichloro-4-iodo-1-methylquinolinium iodide using 3,4,7 trichloroquinoline and methyl iodide; 6,7 dichloro-l ethyl-4-iodoquinolinium iodide using 4,6,7'trichloroquinoline and ethyl iodide; 7- brorno-4-iodo-l methylquinolinium iodide using 4,7-dibromoquinoline, methyl iodide and sodium iodide; 8- chloro-4 iodo 1 isopropylquinolinium iodide using 4,8-dichloroquinoline and isopropyl iodide; 4-iodo-1-npropyl-7-trifiuoromethylquinolinium iodide using 4-chloro- 7-trifluoromethylquinoline and n-propyl iodide; 4 iodol-n-hexyl-B-nitroquinolinium iodide using 4 chloro 3- nitroquinoline and n-hexy-l iodide; 6,8-dimethoxy-1-ethyl- 4-iodoquinolinium iodide using 4-chloro-6,8-dimethoxyquinoline and ethyl iodide; 8-n-butoxy-4-iodo-1-isobutylquinolinium iodide using 8 n-butoxy-4-chloroquinoline and isobutyl iodide; 6-n-hexoxy-4-iodo-1-methylquinolinium iodide using 4-chloro-6-n-hexoxyquinoline and'methyl iodide; l-ethyl 4 iodo-7-methylmercaptoquinolinium iodide using 4-chloro-7 methylmercaptoquinoline and ethyl iodide; l-ethyl 4 iodo-8-isobutylmeroaptoquinolinium iodide using 4-chloro-S-isobutylmercaptoquinoline and ethyl iodide; 7-chloro-4-iodo 6-methoxy-1-methylquinolinium' iodide using 4,7-dichloro-6-methoxyquinoline and methyl iodide; 7-n-butyl-4-iodo-l-methylquinolinium iodide using 7-n-butyl 4 chloroquinoline and methyl iodide; and the like.

B. I -(l0wer-alkyl) 4 [lower-(tertiary-amino)-alkylimino]-1,4-dihydr0quin0lines The preparation of these compounds in the form of their acid-addition salts is illustrated by the following preparation of the hydriodide of 7-ch'loro-4-(2-diethyl aminoethylimino)-1-methyl-1,4-dihydroquinoline: A mixture of 17 g. of 7 chloro-4-iodo-1-methylquinoliniurn iodide and 17.6 g. of Z-diethylaminoethylamine in 250 cc. of anhydrous ethanol was stirred for several minutes and a small amount of insoluble material was removed by filtration. The filtrate was allowed to stand overnight at room temperature and then stirred for about sixteen hours. The solid which separated was collected (10 g.) by filtration. An additional crop (2 g.) was obtained by concentrating the filtrate. This product, 7-chloro-4- (Z-diethylaminoethylimino) l-methyl 1,4 dihydroquinoline hydriodide, melted at 177.0178.4 C. (corn) when recrystallized twice from ethanol.

Anal.-Calcd. for C H ClN fllz I-, 30.22; N, 10.01. Found: 1*, 29.8; N, 9.86.

Other 1-( lower-alkyl) -4- [lower- (tertiary-amino) -alkylimino]-1,4-dihydroquinolines that can be prepared following the above procedure using the appropriate reactants include: 3,7-dichloro-4-(Z-diethylaminoethylimino)- 1-methyl-1,4'dihydroquinoline hydriodide using 3,7-dichloro-4-iodo-1-methylquinolinium iodide and 2-diethylaminoethylamine; 6,7-dichloro-4- [2-( l-piperidyDethyliminol l-ethyl-l,4-dihydroquinoline hydroiodide using 6,7- dichloro-1-ethyl-4-iodoquinolinium iodide and 2-(1- piperidyl)ethy1arnine; 7-bromo-4-(2-di-n-hexylaminoethylimino)-l-methyl-1,4-dihydroquinoline hydriodide using 7-bromo-4-iodo-I-methylquinolinium iodide and 2-di-nhexylaminoethylamine; 8-chloro-4- 3-( 1-pyrrolidy1)propyliminol-1-isopropyl-1,4-dihydroquinoline hydriodide using 8-chloro-4-iodo-l-isopropylquinolinium iodide and" 3 a I I (l-pyrrolidyDpropylamine; 4-(2-diethylaminoethylimino)-1-n propy1-7-trifluoromethyl-1,4-dihydroquinoline hydriodide using. 4-iodo-1-n-propyl 7-trifluoromethylquinolinium iodide and Z-diethylaminoethylamine; 4-[2-(N- ethyl-N-Z-hydroxyethylamino)ethylimino]-1 n hexyl-3- nitrolA-dihydroquinoline hydriodide using 4-iodo-1-nhexyl-3-nitroquinolinium iodide. and 2-(N-ethykN-2- hydroxyethylamino) ethylamine; 6,8-dimethoxy-1-ethyl-4- [2-(4-methyl-1-piperidyl)ethylimino]-l,4 dihydroquino: line hydriodide using 6,8-dimethoxy+1-ethy-4-iodoquinoiodide and 2-' (4-methyl-1-piperidyl) ethylamine; 4- IZ-(N-benzyl-N-ethylamino)ethylimino] 8-n-butoxy 1- isobutyl-1,4:dihydioquinoline hydriodide 7 using 8-n- 'butoxy- 4-iodo-l-isobutylquinolinium iodide and; 2-(N- benzyl-N-ethylamino)ethylamine; 4-(2 dimethylaminoethylimino)-6-n-hexoxy-1-methyl 1,4 dihydroquinoline reacted with aqueous sodium hydroxide solution to yield 7-chloro-4-( 2 diethylaminoethylimino) l-methyl- ,4-dihydroquinoline. EXAMPLE 19 7 -chlom-4-(2 -di ethylc zmir;oethylim inc) -1 -methyl-1,4

dihydroquinoline To a solution containing 3.5 g. of 7-chloro-4-(2-diethy1- aminoethylimino)-1-methyl-1,4-dihydroquinoline hydriochloro-4-iodo-1-methylquinoliniumiiodide, 7.5 g. of 2- methylaminoethylamine and 50 cc. of absolute ethanol, This product was obtained in 60% yield (4.5 g.), MIP; 208210 C. (uncorr.) with decomposition. I

The above-described hydriodide (4 g.) was treated with oneequivalent of alcoholic hydrogen chloride to give the corresponding 'l-chloro-l-methyl-4-(Z-methylaminoethyl imino)-l,4-dihydroquinoline h'ydriodide hydrochloride in solution and the solution was ion-exchanged through 30 g. of an ion-exchange resin saturated with chloride ions (Amberlite IRA-400 resin), said resin suspended in methanol. There was thus obtained 3.1g. (91% yield) of theproduct, 7chloro-1-methy1-4-(Z-methylaminoethyldide in about 5 i) cc. of water was added: an excess of 10% 7 aqueous sodium hydroxide solution. The precipitate was collected, dried and recrystallized from n-hexane to yield the product, '7ch1oro-4 (Q-diethylaminoethylimino)-1- methyl-.1,4-dihydroquinoline, M.P. 77.6-78.8? C. (corn); Anal Calcd. for CwHwClN C, 65.90; H, 7.58; N,

7 14.40. Found: C, 65.60;H,7.46;-N,14.13;

One-half gram of 7-chloro-4-(Z-diethylaminoethylimino) l-methyl-1,4 dihydroquinoline in 20 ec. of acetone Wastreated with twenty drops of 47% aqueous hydriodic acid. The precipitate wascollected and washed with acetone, yielding 1.2 g. of 7f-chloro- 4-(2-diethylamin0-.

ethylimino)-1-methyl-1,4-dihydroquinoline dihydriodide,

M.P. 263264 C. (uncorr.) with decomposition.v

Anal.-Calcd. for C H ClN .2HI:' If, 46.3. Found:

By substitution of the hydriodic acid in the precedingexample with an excess of hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, methanesulfonic.

acid or tartaric acid, there can be obtained '7-chloro.-4-(2 diethylaminoethylimino)-l-methyl-l,4- dihydroquinoline dihydrochloride, dihydrobromide, diphosphate, disulfate,.

dimethanesulfonate or ditartrate, respectively. a

f EXAMPLE 20 V 7-ch loro -l -methy l-4- (Z-methylamirioethylimino) -1,4-' 7 dilzydroquinoline dihydrochloride v 7-chloro- 1-methyl 4-(Z-mthylaininoethylimino) 1,4-

dihydroquinoline hydriodide was prepared'following the procedure described, in Example .1 8B'using 8.6 g.-,of 7

imino)-1,4-dihydroquinoline dihydrochloride, M.P. 283- 285 C; (uncorr.) with decomposition. Recrystallization of this product from isopropanol-absolute ethanol gave 1.7 g.,'M.P. 283.2285.4 C. (corn) with decomposition.

iAnal.--Calcd. for C H C-1N 2HCl: Cl, 21.98; N, 13.02. Found: Cl, 21.56; N,"12.92.

By substitution of the Z-methylaminoethylamine in the preceding example with an equivalent quantity of 4-cyclohexylaminobutylamine, 2 (2 hydroxyethylamino)ethylamine, 3-n-propylaminopropylamine or 2 -n-hexylarninoethylamine, there can be obtained, respectively, -7-chloro- 4-(4-cyclohexylaminobutylimino)-1-methyl 1,4-dihydroquinoline dihydrochloride, '7-ch1oro-4- [2-(2-hydroxyethylamino) ethylimino] -1-methyl- 1,4-dihydroquinoline dihyd'rochlon'de, 7-chloro-1-methyl-4-(S-n-propylaminopropylimino)-1,4-dihydroquinoline dihydrochloride or 7-chloro- 4-(2-n-hexylaminoethylimino) '1 methyl 1,4 dihydroquinoline dihydrochloride. Treatment of these dihydrochlorides with an acid-acceptor according to the procedure described in Example 19 yields the respective compounds in'free base form. I

- EXAMPLE 21 I 7-chlor0-4-[2-(N-Z-chlorobenzyl-N-ethylamina)ethylimino] -1-methyl-1,4-dihydroquinoline hydriodide This preparation was carried outfollowing the procedure described in Example 1813 using 13.0 g. of 7-chloro- 4-iodo l-methylquinolinium .iodide, 19.0 g. of 2 (N-2- chlorobenzyl-N-ethylamino) ethylamine and cc. of anhydrous ethanol. There was thus obtained 14.5 g. (94% yield) of the product, 7 chloro-4-[2-(N-2-chlorobenzyl- N-ethylamino) ethylimino] :-'1 -rnethyl-l ,4-dihydroquinolinehydriodide, M.P..211.0-213.4 C. .(corr.).

Anal.--Calcd. for -c r1, c1,N, .H I= I, 24.62; N, 3.15..

Found: 1", 24.9; N,'7.88.' V

e By substitution of 2-(N-2-chlorobenzyl-N-ethylamino) ethylamine'in'the preceding example by a molar equivalent of- 2-(N 2-nitrobenzy1-N-ethylamino)ethylamine, 2- (N-2,4-dimethoxybenzylrN-ethylamino) ethylarnine, 3-(N- 3-ethylbenzyl-N-rnethylarnino)propylamine, 2-(N 3 tri fluoromethylbenzyl N-ethylamino)'ethylamine, 2 a (N 2- methylmercaptobenzyl N ethylamino) ethylamine or 4-.

(N 2,4,6-trichlorobenzyl N ethylamino)butylamine, there can be obtained," respectively, 7-chloro-4-l2 -(N 2-nitrobenzyl-N-ethylamino)ethyliminol -1- methyl-1,4 dihydroquinoline hydriodide, 7-chloro-4-[2-(N 2,4 dimethoxybenzyl-N-ethylamino) ethylimino] 1 -methyl-1 ,4 dihydroquinoline hydriodide, 7-chloro-4-[3-(N-3-ethylbenzyl-N- methylamino)propylirnino]-1-methyl-l,4-dihydroquinoline a hydriodide, 7 1 chloro-4-l2-(N-3-trifluoromethylbenzyl-N- ethylamino) ethyliminol -1-methyl 1,4 dihydroquinoline hydriodide, 7 -chloro-4-[2-(N-2 methylmercaptobenzyl-N- ethylamino)ethy1imino]-l-rnethyl 1,4 dihydroquinoline hydriodide or" 7-ch1oro-4[4-(N-2,4,fi-trichlorobenzyl-N- ethylamino) butyliminol -1-methyl 1,4 dihydroquinoline' hydriodide. Treatment of these hydriodides with an; acidacceptor yieldsthe corresponding compounds in freebase form, e.g.-, venom- [2-(N-Z-nitrobenzyl-Nwthylamino) ethyliminol lrrnethyl-l,4 dihydroquinoline, etc.

17 7 EXAMPLE 2 7-chloro-1-methyl-4-[2-(4-morphotinyl)ethyliminol-L4- dihydroquinozine hydriodide This preparation was carried out following the procedure described in Example 18A using 4.3 g. of 7-chloro-4- iodo-l-methylquinolinium iodide, 5.2 g. of 2-(4-morpholinyl)ethylamine and 25 cc. of anhydrous ethanol. There was thus obtained 4.3 g. of the product, 7-chloro- 1-methyl-4-[2-(4-rnorpholinyl)ethyliminol-1,4 dihydroquinoline hydriodide, M.P. 243.8-245.6 C. (corr.) when recrystallized from ethanol.

Anal.--Calcd. for C15H2gC1N3O.HI: I, 29.38; N, 9.66. Found: I-, 29.2; N, 9.57.

EXAMPLE 23 7-chl0r0-1 -methyl-4- [2- (1 -piperazz'nyl) ethylimino] -1,4-

dihydroquinoline Following the procedure described in Example 19 using 17.2 g. of 7-chloro-4-iodo-l-methylquinolinium iodide, 20.7 g. of 2-(1-piperazinyl)ethylamine and 120 cc. of anhydrous ethanol, there was obtained 14 g. (81% yield) of 7-chloro-l-methyl-4-[2-(l-piperazinyDethylimino] 1,4- dihydroquinoliue hydriodide.

Treatment of the above-described hydriodide as in Example 19 gave 8.5 g. (88% yield) of 7-chloro-1-methyl-4- [2-(1-piperazinyl)ethyliminol 1,4-dihydroquinoline, M.P. 123.4l26.2 C. (corr.).

Anal.Calcd. for C H ClN Cl, 11.62; N, 18.38. Found: Cl, 11.80; N, 18.43.

EXAMPLE 24 T 1 5 -ch loro-l -m ethyl-4- (2-methylaminoethylimino)-I,4- dihydroquinoline dihydrochloride EXAMPLE 25 5-ch Zr0-4- (Z-diethyZamindethylimino) -1-methyl-1,4- dihydroquinoline dihydriodide Following the procedure described in Example 18B using 12.9 g. of -ehloro-4-iodo-1 methylquinolinium iodide, 13.9 g. of Z-diethylaminoethylamine and 100 cc. of absolute ethanol, there was obtained 3 g. of 5-chloro- 4-'(Z-diethylaminoethylimino) 1 methyl 1,4 dihydroquinoline hydriodide, M.P. 146l49 C. (uncorn) when recrystallized from ethanol.

AnaL-Calcd. for C H ClN .HI: I-, 30.20; N, 10.02. Found: 1', 29.20; N, 9.80.

The above mon'ohydriodide was dissolved in 20 cc. of methanol; 3 cc. of 48% hydriodic acid was added; and the product slowly precipitated. There was thus obtained 2.5 g. of 5-chloro-4-(2-diethylaminoethylimino)-1-methyl- 1,4-dihyclroquinolin'e dihydriodide, M.P. 225.0-227.4 C. (corr.).

Anal.-Calcd. for C H ClN 2HI: 1*, 46.40; N, 7.65. Found: I, 46.25; N, 7.74.

EXAMPLE 26 5-chl0r0-1 -methyl-4- [2-(4-m orpholinyl)ethylimino] -1,4-

Following the procedure described in Example 25 using 13 g. of 5-chloro-4-iodo-l-methylquinolinium iodide, 12

g. of 2-(4-morpholinyl)ethylamine and cc. of anhydrous ethanol, there was obtained 13 g. (99% yield) of 5-chloro-1-rnethyl-4- [2-(4-morpholinyl) ethylimino] 1,4- dihydroquinoline hydriodide, M.P. 187188 C. (uncorn) when recrystallized from methanol. V

' Anal.Calcd. for C H ClN O.H=I: I-, 29.38. Found: H 0, 0.83; I-, 29.15 on). I

The corresponding dihydriodide, prepared as in Example 25, melted at 2480-2502 C. (corr.) when recrystallized from methanol. H

Anal.'Ca1cd. for C H ClN OzHlz I, 45.20; N, 7,48. Found: 1", 45.10; N, 7.29.

EXAMPLE 27 7-chZora-4-(6-a'iethylaminohexylimino)-1-methyZ-1,4- dz'hydroquinoline Following the procedure described in Example 18B using 9.0 g. of 7-chloro-4-iodo-l-methylquinolinium iodide and 6.3 g. of 6-diethylaminohexylamine, there was obtained 6.5 g. (78% yield) of 7-chloro-4-(6-diethylam'inohexylimino)-1-methyl 1,4 dihydroquinoline hydriodide M.P. 179-182 C. (uncorn).

7-chlor0-4-(6-diethylaminohexylimino)-1-methyl 1,4- dihydroquinoline was obtained from the above hydr iodide following the procedure described in Example 19. There was thus obtained 7-chloro-4-(6-diethylarninohexylimino) Lmethyl-l,4-dihydroquinoline,-M.P. 72.4-75.4" C. (corr.) when recrystallized from n-hexane.

Anal.-Ca1cd. for CzoHgoClNgZ NAP, Found: N 8.05; N, 11.93.

EXAMPLE 28 7-chl0r0-4- (1,1-dimethyl-2-isopr0pylamin0ethylimin0)-I- merhyl-1,4dihydr0quin0line hydriodide This preparation was carried out following the procedure described in Example 188 using 14.0 g. 'of 7-ch1oro- 4-iodo-1-methylquinoliniurn iodideand 13.0 g. of 1,1-dimethyl-2-isopropylaminoethylamine. There was thus obtained 4.5 g. of the product, 7-chl0ro-4-(1,1-dimethyl-2- isopropylaminoethylimino) 1 methyl 1,4 dihydroquinoline hyd'riodide, M.P. 2048 2062 C. (corr.) when recrystallized from isopropanol.

Anal.Calcd. for C H C1N l-II: I, 29.26;. N, 9.69.

:Found: I-, 28.9; N, 9.53.

EXAMPLE 29 1-benzyl-4-(Z-diethylaminoethylimino)-1, 4-dihydr0- quinoline hydrochloride Following the procedure described in Example 1B using 7.0 g. of 4-(2-diethylaminoethylan1ino)quinoline, 4.2 g.

of benzyl chloride, 60 cc. of acetonitrile and a reflux period of eighteen hours, there was obtained the product, 1 benzyl 4 '(2 diethylaminoethylimino) 1,4 dihydroquinoline hydrochloride, M.P. 166.2l68.0 C. (corr.) when recrystallized from isopropanol ether.

Anal.-Calcd. for C H N .HCl: Cl", 9.59; N, 11.36. Found: Cl-, 9.62; N, 11.14.

EXAMPLE 30 1-(2-chl0robenzyl)-4-(2-diethylaminoethylimino)-1 ,4- dihydroquinoline hydrochloride Following the procedure described in Example. 1311s ing 5.0 g. of 4-(Z-diethylaminoethylamino)quinoline, 3.2 g. of 2-chlorobenzyl chloride, 25 cc. of acetonitrile and a reflux period of twenty-four hours, there was obtained 2.85 g. of the product, 1-(2-chlorobenzyl)-4-(2-diethylaminoethylimino) 1,4 dihydroquinoline hydrochloride, M.P. 162.0164.6 C. (corr.) when recrystallized twice from ethanol-ethyl acetate. 7

Anal. Calcd. for C H CIN HCl: Cl-, 8.77; N, 10.39. Found: Cl, 8.82; N, 10.23.

.j f n I zemw v EXAMBLE 31' s-ahl a zlmbenz z -4- s-dieth la magro l J imino)-1,4-dihydrquinoline Following the procedure described in Example 6B using ;10.0 g. of S-chloro-l-(Z-chlorobenzyl)-4 iodoquino1inium iodide, 7.5 g. of 3-diethylaminopropy1amine, 150 ml. of

' .ethanol and a heating period of about ten minutes on a .steanrbath, there was obtained 9g. of S-chloro-l-(Z- chlorobenzyl) 4 (3 diethylaminopropylimino) 1,4- dihydroquinoline hydriodide, M.P. l92-193 C. (uncorr.). 7 7

Following the procedure described in Example 2, the above hydriodide was converted into the corresponding iminobase, 5 chloro l (2,-chlorobenzy1) -4 (3 --diethylaminopropylimino) 1,4 1 dihydroquinoline, M.P.

1l4.0-ll5.4 C. (corr.) .when recrystallized from isopropanol. ;-.'Anal.'Calcd. for C23H27C12N32' N 6.74; N, 10.10. Found: N 6.71; N, 10.10. .=-Pharmacologica1 evaluation of the compounds of the invention have shown them to possess hypotensive properties as measured by the serial carotid occlusion procedure in anesthetized dogs. 4

The. compounds of the invention can be formulated for .nsein the same way as conventional hypotensive agents,

' such as reserpine preparations, and indeed can be used advantageously in combination with such agents. They can be formulated into tablets or capsules for oral administrat io n or dissolved ;under sterile conditions for. parenteral injection.

I claim: a

1. A compositioniof matter selected from the group consisting of: (a) a'compoundhaving the formula whereQis selected irom the "g oup consistin of Hiimd from one to two substituents at positions 3, 5, 6, 7 and 8 a '(monocarbocyclic-aryl)methyl, wherein (monocarbocyclic-aryl)methyl in each instance represents a member selected from the group consisting of benzyl, nitroben'zyl, (lower-alkoxylated)-benzyl, v (lower-alkylatedybenzyl, halogenated-benzyl, trifluoromethylbenzyl and (loweralkylmercaptoybenzyl; and, .(b) pharmacodynamically acceptable acid-addition salts thereof. a

" 2. A compound having the structural formula I N-Y- aower-alk l enm f -6 methoxy-1,4-dihydroquinoline.

' 9; A pharmacodynamically acceptable acid-addition :salt. of 4 7.-chloro-4-(Z-diethylamirioethylimino) -1-rnethy1- 2o 7 where Y is lower-alkylene havingits connecting linkages ,on d ifierent carbon atoms, is an integer. from, one to two, Ar is halophenyl and A11 is a pharmacodynamically acceptable anion; Q I i Compound having the stru'ctur'al ioirmula where Y is lower-alkylene having' its connecting linkages ondilferent carbon atoms, m is an integer from one'to two, Ar is halophenyl andAn is a pharmacodynamically acceptable anion. v

1 4. A compound having the structural, formula (halogen) I .mEiAn.

'where Y is lower-alkylene having its connecting linkages on different carbon atoms, m is aninteger from one to two, R is lower-alkyl and An is a pharmacodynamically acceptable anion. r

5. A compound having the structural formula I .niHAn i shes Y is lowr-alkylene'havingitsconnecting'linkages on difierent carbon atoms, AI is halophenyl, m is an in- .tge'r"fr6m"oneatoutwo R is lower-alkyl and An is a pharmacodynamically acceptable'anion;

6. A pharmacodynamically acceptable acid-addition salt of 7-chloro-l-(2 chlorobenzyl) 4-(2-diethylaminoethylimino)-1,4-dihydroquinoline. 7. 7 chlorol (2 -'chlorobenzyl)'- 4 (2 diethylaminoethylimino)-1,4-dihydroquinoline.

"8.'A pharmacodynamically acceptable acid-addition salt of 1-(2-chlorobenzyl)-4-(2-diethylaminoethyliminol- 1,4-dihydroquinoline.

' 1o. 7 chlorcr' 4 (2 diethylaminoethylimino) 1} methyl-1,4-dihydroquinoline.

' A pharmacodynamically acceptable acid-addition salt "of 7 -chloro'-4-[2 (N-ethyl-N-Z-chlorobenzylamino) ethylimino]-l-methyl lA-dihydroquinoline. v V

V References Citedin the file' of this patent" UNITED STATES PATENTS .OTHERREFERENCES I Surrey et al.: 'Jour. Am, Chem, Soc.,' vol. 68, pp.

4 wim l l .l 

1. A COMPOSITION OF MATTER SELECTED FROM THE GROUP CONSISTING OF: (A) A COMPOUND HAVING THE FORMULA 